Departamento de Neurodesarrollo y Fisiología, División Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Distrito Federal, México.
Nat Chem Biol. 2011 Nov 20;8(1):78-85. doi: 10.1038/nchembio.712.
Since 1992, there has been growing evidence that the bioactive phospholipid lysophosphatidic acid (LPA), whose amounts are increased upon tissue injury, activates primary nociceptors resulting in neuropathic pain. The TRPV1 ion channel is expressed in primary afferent nociceptors and is activated by physical and chemical stimuli. Here we show that in control mice LPA produces acute pain-like behaviors, which are substantially reduced in Trpv1-null animals. Our data also demonstrate that LPA activates TRPV1 through a unique mechanism that is independent of G protein-coupled receptors, contrary to what has been widely shown for other ion channels, by directly interacting with the C terminus of the channel. We conclude that TRPV1 is a direct molecular target of the pain-producing molecule LPA and that this constitutes, to our knowledge, the first example of LPA binding directly to an ion channel to acutely regulate its function.
自 1992 年以来，越来越多的证据表明，生物活性磷脂溶血磷脂酸（LPA）在组织损伤时会增加，它可以激活初级伤害感受器，导致神经病理性疼痛。瞬时受体电位香草酸亚型 1（TRPV1）离子通道表达于初级传入伤害感受器，可被物理和化学刺激激活。在这里，我们发现 LPA 在对照小鼠中产生急性痛觉样行为，而在 TRPV1 基因敲除小鼠中则明显减少。我们的数据还表明，LPA 通过一种独特的机制激活 TRPV1，该机制与 G 蛋白偶联受体无关，与其他离子通道的广泛表现相反，通过直接与通道的 C 末端相互作用。我们得出结论，TRPV1 是产生疼痛的分子 LPA 的直接分子靶标，据我们所知，这是 LPA 直接结合离子通道以急性调节其功能的第一个例子。
